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Background: Glioblastoma initiation and progression is believed to be driven by Glioma stem cells (GSCs). Activation of NOTCH1 and WNT, and more recently, non-canonical WNT5A signaling, has been demonstrated to regulate self-renewal and differentiation of the GSCs crucially. High expression levels of NOTCH1 and WNT in GBM tumors contribute to the sustenance of GSCs and mediate characteristic phenotypic plasticity, which is reflected by the different subtypes and tremendous intra-tumor heterogeneity. However, the coregulation of NOTCH1 and WNT5A is not well understood. Here, we studied the role of these molecules in regulating the characteristics of different GSC subtypes., Methods: We established a novel GSC-enriched cell model, referred to as NSG-70, from a patient with recurrent GBM. NSG-70 cells harbor a unique cytogenetic feature, viz. isochromosome 9q. At the same time, its expression profiles indicate that it is a mixed lineage comprising proneural and mesenchymal subtypes. We examined the relevance of NOTCH1 and WNT5A signaling and their coordinated action in GBM using these cells and other patient-derived models representing different GSC subtypes., Results: Our data revealed that the downregulation of NOTCH1 resulted in the suppression of stem cell and mesenchymal markers and significantly reduced the levels of WNT5A. NOTCH1 knockdown also led to a notable reduction in the vasculogenic mimicry of GSCs. Interestingly, knockdown of WNT5A exhibited similar effects and drove quiescent GSC towards proliferation. In a complementary manner, ectopic expression of WNT5A or rhWNT5A treatment rescued the effects of NOTCH1 knockdown., Conclusion: The resistance of GSCs towards conventional therapies in part due to subtype interconversion demands therapies targeting specific GSC subtype. Our study suggests the need for a combinatorial approach that could effectively target the NOTCH1-WNT5A signaling axis toward eliminating GSCs., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

RNA-binding proteins (RBPs) are critical players in the post-transcriptional regulation of gene expression and are associated with each event in RNA metabolism. The term 'RNA-binding motif' (RBM) is assigned to novel RBPs with one or more RNA recognition motif (RRM) domains that are mainly involved in the nuclear processing of RNAs. RBM47 is a novel RBP conserved in vertebrates with three RRM domains whose contributions to various aspects of cellular functions are as yet emerging. Loss of RBM47 function affects head morphogenesis in zebrafish embryos and leads to perinatal lethality in mouse embryos, thereby assigning it to be an essential gene in early development of vertebrates. Its function as an essential cofactor for APOBEC1 in C to U RNA editing of several targets through substitution for A1CF in the A1CF-APOBEC1 editosome, established a new paradigm in the field. Recent advances in the understanding of its involvement in cancer progression assigned RBM47 to be a tumor suppressor that acts by inhibiting EMT and Wnt/[Formula: see text]-catenin signaling through post-transcriptional regulation. RBM47 is also required to maintain immune homeostasis, which adds another facet to its regulatory role in cellular functions. Here, we review the emerging roles of RBM47 in various biological contexts and discuss the current gaps in our knowledge alongside future perspectives for the field., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The concept of cancer as a stem cell disease has slowly gained ground over the last decade. A 'stem-like' state essentially necessitates that some cells in the developing tumor express the properties of remaining quiescent, self-renewing and regenerating tumors through establishment of aberrant cellular hierarchies. Alternatively, such capacities may also be reacquired through a de-differentiation process. The abnormal cellular differentiation patterns involved during either process during carcinogenesis are likely to be driven through a combination of genetic events and epigenetic regulation. The role(s) of the latter is increasingly being appreciated in acquiring the requisite genomic specificity and flexibility required for phenotypic plasticity, specifically in a context wherein genome sequences are not altered for differentiation to ensue. In this chapter, the recent advances in elucidating epigenetic mechanisms that govern the self-renewal, differentiation and regenerative potentials of cancer stem cells will be presented.

Immature embryos of thirty-three genotypes of wheat were cultured on 2,4-D containing medium. Occurrence of precocious germination of the zygotic and somatic embryos simultaneously on the same medium was a striking feature observed during the course of work. The percentage of precocious germination was seen to vary extensively from 0-88% and 0-84% for zygotic and somatic embryos respectively. In the genotypes NI-5439 and NI-5643 which are characterized by a high tillering capacity, the phenomenon of precocious germination seems to take a different path from that observed in the other genotypes. This is evident since these two genotypes require total absence of hormone for shoot elongation although multiple shoot primordia are formed on auxin containing medium.Precocious germination also seems to be relevant to somatic embryogenesis and plantlet regeneration. This conclusion stems from the observation that a majority of the genotypes that show precocious germination of zygotic embryos have greater embryogenic potential. Consecutively, most of the genotypes that show precocious germination of somatic embryos exhibit a higher frequency and faster rate of plantlet regeneration.